Prostate Cancer
Conditions
Keywords
prostate cancer, prostate, immune therapy, immunotherapy, vaccine, dendritic cells, antigen-presenting cells, antigen presenting cells, cancer vaccine, prostate specific antigen (PSA), prostatic adenocarcinoma
Brief summary
This is a randomized, multicenter, single blind, Phase 2 trial of immunotherapy in men with metastatic androgen independent prostate cancer to evaluate sipuleucel-T manufactured with different concentrations of PA2024 antigen
Detailed description
This is a randomized, multicenter, single blind, Phase 2 trial of immunotherapy in men with metastatic androgen independent prostate cancer to evaluate sipuleucel-T manufactured with 1 of 3 different concentrations of PA2024 antigen The primary purpose of this study is to compare the changes in CD54 upregulation between each of these 3 groups of subjects.
Interventions
BIOLOGICALsipuleucel-T
Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF)
Sponsors
Dendreon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For a subject to be eligible for participation in this study, all of the following criteria must be satisfied. * Histologically documented adenocarcinoma of the prostate. * Metastatic disease. * Progressive androgen independent castrate resistant prostate cancer. * Serum PSA ≥ 5.0 ng/mL. * Life expectancy of ≥ 6 months. * Castrate level of testosterone (\< 50 ng/dL) achieved via medical or surgical castration. * Men ≥ 18 years of age. * Adequate hematologic, renal and liver function.
Exclusion criteria
A subject will not be eligible for participation in this study if any of the following criteria apply. * The presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites. * A requirement for treatment with opioid analgesics for any reason within 21 days prior to registration. * Moderate to severe disease related pain. * Eastern Cooperative Oncology Group (ECOG) performance status ≥ 2. * Use of non-steroidal antiandrogens within 6 weeks of registration. * Anti-androgen withdrawal response. * Treatment with chemotherapy within 3 months of registration. * More than 2 chemotherapy regimens prior to registration. * Initiation or discontinuation of bisphosphonate therapy within 28 days prior to registration. * Treatment with any of the following medications or interventions within 28 days of registration: * Systemic corticosteroids, * External beam radiation therapy or surgery, * Dietary and herbal supplements, as well as alternative treatments that have evidence of hormonal and/or anticancer properties (e.g., prostate cancer (PC) -SPES or PC-SPEC) and saw palmetto, * Megestrol acetate (Megace®), diethylstilbesterol (DES), or cyproterone acetate, ++Ketoconazole, * 5-alpha-reductase inhibitors, * High dose calcitriol \[1,25(OH)2Vitamin D\] (i.e., \> 0.5 mcg/day). * Any other systemic therapy for prostate cancer (except for medical castration). * Treatment with any investigational vaccine within 2 years of registration or treatment with any other investigational product within 28 days of registration. * Participation in any previous study involving sipuleucel-T, regardless of whether the subject received sipuleucel-T (APC8015) or placebo. * Known pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography \> 50%) or spinal cord compression. * A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous cell skin cancers must have been adequately treated and the subject must be disease-free at the time of registration. Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years at the time of registration. * A requirement for systemic immunosuppressive therapy for any reason. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or granulocyte-macrophage colony-stimulating factor. * Any infection requiring parenteral antibiotic therapy or causing fever (temp \> 100.5°F or \> 38.1°C) within 1 week prior to registration. * Any medical intervention or other condition which, in the opinion of the Principal Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative CD54 Upregulation Ratio Between Each of the Cohorts. | Baseline, Months 2, 4 and 6. | An analysis of variance model for the log transformed cumulative CD54 upregulation ratio (CD54 upregulation is the fold increase in the final product (FP) from buoyant density separations (BDS) step 65. BDS65 step refers to sample taken after both BDS77 and BDS65 but before ex vivo culture in the presence of antigen PA2024. FP refers to sample taken after ex vivo culture) that includes the antigen concentration cohort as the independent variable was performed. Subjects who received all 3 infusions were included. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Sipuleucel-T with the concentration of 10 μg/mL PA2024 in a cell suspension of 1 x 10\^7 PBMCs per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions. | 41 |
| Cohort B Sipuleucel-T with the concentration of 5 μg/mL PA2024 in a cell suspension of 1 x 10\^7 PBMCs per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions. | 40 |
| Cohort C Sipuleucel-T with the concentration of 2 μg/mL PA2024 in a cell suspension of 1 x 10\^7 PBMCs per mL. Subjects received infusion of sipuleucel-T, at 2-week intervals, for a total of 3 infusions. | 41 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 29 | 36 | 36 |
| Overall Study | Unable to start due to disease prog. | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort C | Total | Cohort A | Cohort B |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 91 Participants | 30 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 31 Participants | 11 Participants | 9 Participants |
| Age, Continuous | 68.6 years STANDARD_DEVIATION 7.5 | 70.5 years STANDARD_DEVIATION 8.07 | 71.0 years STANDARD_DEVIATION 8.25 | 71.8 years STANDARD_DEVIATION 8.29 |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 0=Fully Active; No restrictions | 27 Participants | 80 Participants | 29 Participants | 24 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 1= Restricted Strenuous Activity | 14 Participants | 42 Participants | 12 Participants | 16 Participants |
| Gleason Score Gleason Score ≤ 6 | 4 Participants | 19 Participants | 7 Participants | 8 Participants |
| Gleason Score Gleason Score =7 | 14 Participants | 41 Participants | 12 Participants | 15 Participants |
| Gleason Score Gleason Score ≥ 8 | 23 Participants | 61 Participants | 22 Participants | 16 Participants |
| Gleason Score Missing information | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 111 Participants | 38 Participants | 35 Participants |
| Region of Enrollment United States | 41 Participants | 122 Participants | 41 Participants | 40 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 41 Participants | 122 Participants | 41 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 29 / 40 | 36 / 40 | 36 / 40 |
| other Total, other adverse events | 38 / 40 | 40 / 40 | 40 / 40 |
| serious Total, serious adverse events | 10 / 40 | 9 / 40 | 11 / 40 |
Outcome results
Primary
Cumulative CD54 Upregulation Ratio Between Each of the Cohorts.
An analysis of variance model for the log transformed cumulative CD54 upregulation ratio (CD54 upregulation is the fold increase in the final product (FP) from buoyant density separations (BDS) step 65. BDS65 step refers to sample taken after both BDS77 and BDS65 but before ex vivo culture in the presence of antigen PA2024. FP refers to sample taken after ex vivo culture) that includes the antigen concentration cohort as the independent variable was performed. Subjects who received all 3 infusions were included.
Time frame: Baseline, Months 2, 4 and 6.
Population: Cumulative CD54 upregulation ratio will be the primary end point and calculated as the sum of Infusion 1 through Infusion 3 final product values for each infused subject.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A | Cumulative CD54 Upregulation Ratio Between Each of the Cohorts. | 29.53 Ratio ofCD54 molecules on BDS65:FP cells | Standard Error 1.285 |
| Cohort B | Cumulative CD54 Upregulation Ratio Between Each of the Cohorts. | 30.94 Ratio ofCD54 molecules on BDS65:FP cells | Standard Error 1.418 |
| Cohort C | Cumulative CD54 Upregulation Ratio Between Each of the Cohorts. | 26.67 Ratio ofCD54 molecules on BDS65:FP cells | Standard Error 1.194 |
Comparison: The sample size determination is based on a standard deviation of 0.45 for the log transformed CD54 upregulation ratio estimated from previous studies assuming there is no difference in central values between the two compared cohorts. A sample size of 38 subjects per cohort will provide 70% power for the non-inferiority test for the two pairwise comparisons (Cohort B vs. Cohort A and Cohort C vs. Cohort A).p-value: 0.501990% CI: [0.936, 1.168]ANOVA
Comparison: The sample size determination is based on a standard deviation of 0.45 for the log transformed CD54 upregulation ratio estimated from previous studies assuming there is no difference in central values between the two compared cohorts. A sample size of 38 subjects per cohort will provide 70% power for the non-inferiority test for the two pairwise comparisons (Cohort B vs. Cohort A and Cohort C vs. Cohort A).p-value: 0.144390% CI: [0.813, 1.013]ANOVA